The current methods of quantitating regional myocardial perfusion in humans are limited. Myocardial contrast echocardiography (MCE) is a developing technique that utilizes state-of-the-art ultrasound technology coupled with the injection of precision microbubbles of air into the circulation. As these bubbles traverse the myocardium, they produce contrast enhancement on echocardiography which can be quantitated. The aim of the current research program is to quantitate regional myocardial blood flow in the beating heart using MCE and to derive pathophysiologic insight from this information into acute and chronic ischemic syndromes in humans. The specific aims of this research program in relation to MCE are: a) Quantitation of myocardial blood flow in-vivo in the beating canine and human heart; b) Transpulmonary opacification of the myocardium from a venous injection of contrast and studying its role during coronary occlusion and reperfusion; c) Assessment of myocardial viability in patients with acute myocardial infarction and those with 'hibernating myocardium' (multi-vessel disease and reduced left ventricular function) and comparing this information to that obtained on thallium-201 imaging; d) Risk-stratification of patients undergoing major vascular surgery based on their myocardial perfusion patterns during venous injection of contrast and comparing this information to that obtained on thallium-201 imaging; and, e) Assessment of coronary blood flow reserve in both dogs and humans from intra-aortic injection of contrast (in humans, prior to and following coronary angioplasty). The ultimate goal of this proposal is the quantitation of regional myocardial flow-function relations in humans using MCE in order to better understand pathophysiology in various ischemic syndromes. In order to better control the experimental conditions, studies will first be performed in canine models prior to deriving information from patients. Validation of microbubble transit rates will be performed with radiolabeled red cells and regional myocardial blood flow with radiolabeled microspheres. Infarct size will be measured using vital stains and risk area will be assessed using technetium autoradiography. Quantitative MCE will be performed using image analysis techniques and mathematical modeling based on indicator-dilution principles. In patients, perfusion will be compared against thallium-201 images and parameters of blood flow reserve will be compared with intravascular ultrasound images and quantitative coronary angiography.